Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis.
We have demonstrated that ginsenoside Rh2 (G-Rh2), a ginseng saponin with a dammarane skeleton, induces apoptosis of human hepatoma SK-HEP-1 cells as evidenced by analyses of DNA fragmentation, flow cytometry and changes in cell morphology. Ac-YVAD-CMK or Ac-DEVD-CHO effectively prevented G-Rh2-induced DNA fragmentation, indicating the involvement of caspase-like proteases in the process of apoptosis. In addition, G-Rh2 induced the processing of caspase-3 to an active form, p17. In stable Bcl-2 transfectants, G-Rh2 also induced DNA fragmentation, while staurosporine-induced DNA fragmentation was totally blocked. As it did in wild-type cells, G-Rh2 induced the proteolytic activation of caspase-3 protease and subsequent cleavage of PARP in the bcl-2 transfectants. In summary, G-Rh2 contains an apoptotic inducing activity in SK-HEP-1 cells which functions via Bcl-2-insensitive activation of caspase-3, followed by proteolytic cleavage of PARP.
Park
J A
JA
Department of Molecular Biology, College of Natural Science, Pusan National University, South Korea.
Lee
K Y
KY
Oh
Y J
YJ
Kim
K W
KW
Lee
S K
SK
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D010450:Endopeptidases / Q000096:biosynthesis*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005434:Flow Cytometry; D036145:Ginsenosides; D006801:Humans; D005894:Panax / Q000502:physiology; D010946:Plants, Medicinal; D011480:Protease Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D004365:Drugs, Chinese Herbal; D004792:Enzyme Precursors; D036145:Ginsenosides; D011480:Protease Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; C055305:ginsenoside Rh2; D010450:Endopeptidases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D019311:Staurosporine